RESUMO
The function of dNTP hydrolase SAMHD1 as a viral restriction factor to inhibit the replication of several viruses in human immune cells was well established. However, its regulation and function in lung cancer have been elusive. Here, we report that SAMHD1 is down regulated both on protein and mRNA levels in lung adenocarcinoma compared to adjacent normal tissue. We also found that SAMHD1 promoter is highly methylated in lung adenocarcinoma, which may inhibit its gene expression. Furthermore, over expression of the SAMHD1 reduces dNTP level and inhibits the proliferation of lung tumor cells. These results reveal the regulation and function of SAMHD1 in lung cancer, which is important for the proliferation of lung tumor cells.
Assuntos
Adenocarcinoma/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Adenocarcinoma/genética , Linhagem Celular Tumoral , Metilação de DNA , Regulação para Baixo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Proteínas Monoméricas de Ligação ao GTP/genética , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Proteína 1 com Domínio SAM e Domínio HDRESUMO
OBJECTIVE: To evaluate the correlation between programmed death-ligand 1 (PD-L1) expression in primary lung cancer cells, tumor associated macrophages (TAM) and patients' clinicopathological characteristics. METHODS: From 2008 to 2010, 208 non-small cell lung cancer patients who underwent surgery or CT-guided biopsy were recruited from Huadong Hospital, Fudan University. Immunohistochemistry staining was performed to evaluate the PD-L1 expression in both primary lung cancer cells and CD68 positive TAM. The relationship between PD-L1 expression and the clinical pathology was evaluated using χ(2) test. Spearman's rank correlations were used to determine the correlation between PD-L1 expression in tumor cells and macrophages. RESULTS: Positive PD-L1 expression in primary cancer cells was found in 136 (65.3%) patients, which were negatively correlated with lymph node metastasis (P=0.009) and smoking history (P=0.036). Besides, TAM with PD-L1 expression (found in 116 patients) was positively associated with smoking history (P=0.034), well-differentiation (P=0.029) and negative lymph node metastasis (P=0.0096). A correlation between PD-L1 expression in primary tumor cells and non-small cell lung cancer associated macrophages was found (r=0.228, P=0.021). CONCLUSION: PD-L1, secreted from TAM, might induce cancer cells apoptosis, and decrease lymph node metastasis.
Assuntos
Apoptose , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Macrófagos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metástase Linfática , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
INTRODUCTION: X-ray repair cross-complementing protein 3 (XRCC3) is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy. METHODS: A systematic review and meta-analysis was performed to evaluate the predictive value of XRCC3 Thr241Met polymorphism on clinical outcomes of advanced NSCLC receiving platinum-based chemotherapy. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: A number of 11 eligible studies were identified according to the inclusion criteria. Carriers of the variant XRCC3 241Met allele were significantly associated with good response to platinum-based chemotherapy (ThrMet/MetMet vs. ThrThr: OR â=â1.509, 95% CI: 1.099-2.072, Pheterogeneity â=â0.618). The XRCC3 Thr241Met polymorphism was not associated with OS (MetMet vs. ThrThr, HR â=â0.939, 95% CI:0.651-1.356, Pheterogeneity â=â0.112) or PFS (MetMet vs. ThrThr, HR â=â0.960, 95% CI: 0.539-1.710, Pheterogeneity â=â0.198). Additionally, no evidence of publication bias was observed. CONCLUSIONS: This systematic review and meta-analysis shows that carriers of the XRCC3 241Met allele are associated with good response to platinum-based chemotherapy in advanced NSCLC, while the XRCC3 Thr241Met polymorphism is not associated with OS or PFS.
